Graphical Abstract:

Abstract:

Background: Many CNS drugs have low bioavailability due to their poor water solubility of
extensive first-pass metabolism and hence have less effectiveness.

Objective: The present study aims to enhance the solubility and oral bioavailability of poorly watersoluble
antipsychotic drug Amisulpride (AMS) through complexation with 2-hydroxypropyl β-
cyclodextrin (HPβCD). It has slow and erratic absorption after oral administration.

Methods: This report describes the study of the phase solubility diagram, preparation of the inclusion
complex and tablet of prepared inclusion complex, characterization of the physico-chemical properties
of the inclusion complex and tablet.

Results: In-vitro study (100 % drug release in 15 minutes), and in-vivo study of an AL-type (linear type)
phase solubility diagram indicated a complex of AMS-HP-β-CD with the constant complex formation
of 13245 M−1 at 37°C. The complex formation was confirmed by DSC, IR, and X-ray diffraction. The
extent of absorption of the complex was determined in rats and was compared with that of pure drug
and the market product. The peak plasma concentration of pure drug was 30.05 ± 1.3 ng/ml (Cmax) at 60
± 3 min, whereas with the market product the value was 54.85 ± 1.2 ng/ml at 40 ± 1 min and with
AMS-HPβCD inclusion complex the value was 79.01 ± 1.5 ng/ml. The AUCtot of the pure drug was
2980.34±3.6, the market product was 7238.73±2.9 and of the inclusion complex was 11871.1±2.8.

Conclusion: Pharmacodynamic studies in mice showed improved effectiveness of drug compared to
pure drug. The oral bioavailability of AMS was improved from 48% to 78%.

Abstract:Background: Many CNS drugs have low bioavailability due to their poor water solubility of
extensive first-pass metabolism and hence have less effectiveness.

Objective: The present study aims to enhance the solubility and oral bioavailability of poorly watersoluble
antipsychotic drug Amisulpride (AMS) through complexation with 2-hydroxypropyl β-
cyclodextrin (HPβCD). It has slow and erratic absorption after oral administration.

Methods: This report describes the study of the phase solubility diagram, preparation of the inclusion
complex and tablet of prepared inclusion complex, characterization of the physico-chemical properties
of the inclusion complex and tablet.

Results: In-vitro study (100 % drug release in 15 minutes), and in-vivo study of an AL-type (linear type)
phase solubility diagram indicated a complex of AMS-HP-β-CD with the constant complex formation
of 13245 M−1 at 37°C. The complex formation was confirmed by DSC, IR, and X-ray diffraction. The
extent of absorption of the complex was determined in rats and was compared with that of pure drug
and the market product. The peak plasma concentration of pure drug was 30.05 ± 1.3 ng/ml (Cmax) at 60
± 3 min, whereas with the market product the value was 54.85 ± 1.2 ng/ml at 40 ± 1 min and with
AMS-HPβCD inclusion complex the value was 79.01 ± 1.5 ng/ml. The AUCtot of the pure drug was
2980.34±3.6, the market product was 7238.73±2.9 and of the inclusion complex was 11871.1±2.8.

Conclusion: Pharmacodynamic studies in mice showed improved effectiveness of drug compared to
pure drug. The oral bioavailability of AMS was improved from 48% to 78%.